Trifluoroacetic acid → HCID 89649345, compound

HRID 2207656Notes

Reaction equation

HRID 2207656 reaction equation
[CH3:1][N:2]1[CH2:26][CH2:25][C@:4]2([N:8]=[C:7]([C:9]3[CH:14]=[C:13]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=4)[CH:12]=[CH:11][N:10]=3)[CH2:6][CH2:5]2)[C:3]1=[O:27].[B-](F)(F)(F)[F:29].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1.FC(F)(F)C(O)=O.[OH-].[Na+]>CC#N>[F:29][CH:6]1[CH2:5][C@@:4]2([CH2:25][CH2:26][N:2]([CH3:1])[C:3]2=[O:27])[N:8]=[C:7]1[C:9]1[CH:14]=[C:13]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:20]=2)[CH:12]=[CH:11][N:10]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 2724933SelectfluorHCID 89649163HCID 89649163, compound

Product 1

HCID 89649345HCID 89649345, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

Anhydrous MeCN (5 mL) was added to a dry vial charged with (5S)-7-methyl-2-[4-[4-(trifluoromethyl)phenyl]-2-pyridyl]-1,7-diazaspiro[4.4]non-1-en-6-one (which may be prepared as described in Description 118) (339.99 mg, 0.9100 mmol). Selectfluor (1500 mg, 4.23 mmol) was added to the solution followed by trifluoroacetic acid (0.04 mL, 0.5300 mmol). The vial was sealed under nitrogen and was heated to 90° C. for 24 h. The reaction mixture was allowed to cool to room temperature whence it was poured onto 0.5M sodium hydroxide. The mixture was left to stir for 10 min and extracted with ether. The combined organic layer was dried (sodium sulfate), filtered and the filtrate was evaporated to give an amber oil. The crude residue was purified by silica gel chromatography (10 g SiO2) eluting with ethyl acetate in iso-hexane (10-100%). Evaporation of desired fractions gave (5R)-3-fluoro-7-methyl-2-[4-[4-(trifluoromethyl)phenyl]-2-pyridyl]-1,7-diazaspiro[4.4]non-1-en-6-one, as an amber oil, a 2:1 mixture of epimers. The isomers were separated by chiral semi-prep hplc using a ChiralPak AD-H column eluting with ethanol/n-heptane (20%:80%) to obtain a faster running epimer (D119a) (28 mg);

Workup

  1. customThe vial was sealed under nitrogen
  2. temperatureto cool to room temperature whence it
  3. waitThe mixture was left
  4. extractionextracted with ether
  5. dry with materialThe combined organic layer was dried (sodium sulfate)
  6. filtrationfiltered
  7. customthe filtrate was evaporated
  8. customto give an amber oil
  9. customThe crude residue was purified by silica gel chromatography (10 g SiO2)
  10. washeluting with ethyl acetate in iso-hexane (10-100%)
  11. customEvaporation of desired fractions

Sources & evidence

ORD record
ord-bfbdbabe49a44d5f916bfffad1d961d9
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

Loading…